Altering FGF8/17 signaling in the embryonic cortex causes a rearrangement of the cortical area map. Depending on the exact experimental condition, individual areas and regions can be shrunken or expanded, shifted or duplicated following FGF8/17 manipulations. Nonetheless, initial morphology of individual areas appears normal; moreover, correct thalamic axons find their repositioned targets. We now plan to examine the long-term effects of rearranging the cortical area map. Our overall hypothesis is that alterations in cortical anatomy and function will emerge over time as a result of early changes in the area map. We expect that our findings will help to shed light on how basic organization of cerebral cortical function is set up in development. We plan to generate a series of mouse lines in which progressive loss of FGF8/17 signaling leads to a progressive decrease in anterior cortex. These findings should further characterize the role of FGF8/17 signaling in anterior-posterior (A/P) patterning of the cortex. We will then determine which receptors are involved in Fgf8/17 signaling by conditionally deleting floxed Fgf receptor genes in the cortical primoridum. Our prediction is that loss of two or more Fgf receptors will phenocopy reduction of Fgf8. Finally, we will cross mutant mouse lines to delete, sequentially, one or both alleles of the genes encoding Emx2, Fgf8, Fgf17. Findings should help identify interactions between telencephalic Fgf8 and some of the transcription factors implicated in area patterning. [unreadable] [unreadable]